Spencer R L, Miller A H, Moday H, McEwen B S, Blanchard R J, Blanchard D C, Sakai R R
Department of Psychology, University of Colorado, Boulder 80309, USA.
Psychoneuroendocrinology. 1996 Jan;21(1):95-109. doi: 10.1016/0306-4530(95)00020-8.
Adult male and female rats were housed for 2 weeks in a Visible Burrow System resulting in the development of strong dominant-subordinate relationships among the male rats. Neuroendocrine measures indicated that the subordinate rats, and to a lesser extent dominant rats, experienced chronic HPA axis hyperstimulation during the 2 week experience. This paper focuses on the consequences of this chronic social stress on cytosolic type II corticosteroid receptor binding in the spleen. In the first study, rats were adrenalectomized 18 h prior to sacrifice in order to measure total cellular receptor protein levels in each animal. In spite of the severity of the social stress, there was no decrease in splenic type II corticosteroid receptor binding levels in these short-term adrenalectomized animals. In the second study, rats were left adrenal-intact. Corticosteroid receptor levels in these adrenal-intact animals reflect the level of receptors (available receptors) that were unoccupied by endogenous hormone at the time of sacrifice. Both subordinate and dominant rats had fewer available splenic type II receptors than control rats, suggesting that a greater proportion of receptors in subordinate and dominant rats were occupied and activated by endogenous hormone at the time of sacrifice than in control rats. The differences in available receptor levels were not a function of total plasma corticosterone levels at the time of sacrifice (mean corticosterone levels were the same for control and subordinate rats). Instead, the differences in available receptor levels may have been a function of plasma corticosteroid binding globulin (CBG) levels which regulate free corticosterone levels. There was a large reduction in plasma CBG levels of subordinate (-70%) and dominant (-40%) rats relative to control rats, and there was a significant correlation between plasma CBG level and available type II receptors in the spleen. These results suggest that a decrease in CBG levels as a result of chronic social stress led to greater access of free corticosterone hormone to type II receptors in the spleen than is typically present in rats under basal or acute stress conditions. This result illustrates one mechanism by which chronic stress may have a greater impact than acute stress on splenic immune function.
成年雄性和雌性大鼠被安置在可见洞穴系统中饲养2周，导致雄性大鼠之间形成了强烈的主导-从属关系。神经内分泌指标表明，在这2周的经历中，从属大鼠以及程度较轻的主导大鼠经历了慢性HPA轴过度刺激。本文重点关注这种慢性社会应激对脾脏中细胞溶质型II皮质类固醇受体结合的影响。在第一项研究中，大鼠在处死前18小时进行肾上腺切除术，以测量每只动物的总细胞受体蛋白水平。尽管社会应激严重，但在这些短期肾上腺切除的动物中，脾脏型II皮质类固醇受体结合水平并未降低。在第二项研究中，大鼠保留肾上腺完整。这些肾上腺完整动物的皮质类固醇受体水平反映了处死时未被内源激素占据的受体水平（可用受体）。从属和主导大鼠的脾脏可用型II受体均比对照大鼠少，这表明与对照大鼠相比，从属和主导大鼠在处死时更多比例的受体被内源激素占据并激活。可用受体水平的差异不是处死时血浆总皮质酮水平的函数（对照和从属大鼠的平均皮质酮水平相同）。相反，可用受体水平的差异可能是调节游离皮质酮水平的血浆皮质类固醇结合球蛋白（CBG）水平的函数。与对照大鼠相比，从属（-70%）和主导（-40%）大鼠的血浆CBG水平大幅降低，并且血浆CBG水平与脾脏中可用型II受体之间存在显著相关性。这些结果表明，慢性社会应激导致的CBG水平降低，使游离皮质酮激素比基础或急性应激条件下的大鼠更易接触到脾脏中的II型受体。这一结果说明了慢性应激可能比急性应激对脾脏免疫功能产生更大影响的一种机制。
